Research directed to the development of active ingredients suitable for the treatment of anxiety is one of the most important fields of pharmaceutical research. The reason of this is that the occurrence of anxiety is extremely high in normal populations. According to statistics the ratio of anxiety is generally 4–10% per year but pursuant to certain estimations it can even reach 20% of the population [Ad Sitsen, J. M., Current Trends in Anxiolytic Research, Scrip, (1992) March].
Anxiety is not a separate disease entity but rather a generic term which encompasses groups of psychiatric clinical patterns (generalized anxiety disorder, panic disease, compulsive disorder, post-traumatic stress disorder etc.). For the time being the most accepted diagnostic system for the classification of anxiolytic clinical pictures is the DSM-IV system published by the American Psychiatric Society.
For the treatment of anxiety disorders most widespreadly compounds having a benzodiazepine structure and compounds having no benzodiazepine structure but binding to the GABA-benzodiazepine-Cl− ion complex (e.g. diazepam, alprazolam, meprobamat, clonazepam) are used. Benzodiazepine type anxiolytics are accompanied, however, by several undesired side-effects (e.g. sedation, muscle relaxant effect, dependency etc.) Said side-effects influence the quality of life of the patients in an adverse manner. Besides benzodiazepine type medicines only a few other active ingredients are commercially available (e.g. buspiron) which enable alternative treatment. In case of buspiron therapeutical effect can be achieved only after a treatment lasting for at least 12–14 days.
Neuroleptic 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazole derivatives are described in J. Med. Chem., 28(6), 761–769 (1985). Antiarrhythmic 3(2H)-pyridazinone derivatives are known from U.S. Pat. No. 5,395,934.